Acute myocardial infarction (AMI) is a serious threat to human health. It is one of the most main diseases that lead to mortality and disability. Quick diagnosis of early acute myocardial infarction combined with timely treatment is the key to reducing patient mortality. For patients who do not experience typical chest pain or whose electrocardiography do not show obvious changes, it is difficult to be accurately diagnosed by solely relying on EKG, echocardiography and cardiac magnetic resonance. Therefore, detecting serum cardiac markers are necessary criteria for diagnosing of AMI.
The cardiac markers are a series of biochemical substances that can be measured in the blood, and are cardiac-specific, and are released in large quantity into the patients' blood circulation when patients experience myocardial injury, and can diagnose myocardial injury by measuring changes of their concentration levels in the blood, thus can be used as monitoring markers for screening, diagnosing, and evaluating prognosis and treatments for myocardial injury. Various cardiac markers have been consistently discovered in clinical practice that indicate myocardial injury, including indicators for myocardial ischemic injury such as Ischemia Modified Albumin and myeloperoxidase etc., and indicators for myocardial necrosis such as cardiac troponin etc. Cardiac markers provide convenience for clinic that enhances the diagnosis and prognosis for myocardial injury.
AMI happens in a short time and does not possess specific precursor symptoms. It is typically difficult to timely diagnose AMI, especially in early stage. Therefore, only the cardiac markers that increase rapidly during the early stage can be used as a warning sign, so that patients can receive timely medical rescue to avoid myocardial damage. In recent years, clinical studies has shown that Heart-type fatty acid binding protein (H-FABP) and myeloperoxidase (MPO) are closely linked to the diagnosing and predicting AMI risk of the patients with acute coronary syndrome. They are new markers for predicting risk of myocardial damage.
Myeloperoxidase (MPO) is a marker for atherosclerosis lesion instability and stress reaction of neutrophils as well as a risk prediction of AMI. MPO is a type of peroxidase that mainly exists in the azurophilic granule of neutrophils or monocyte. Neutrophils will be activated during inflammation, degranulated and released MPO. This can lead to the coronary artery atherosclerotic lesions instability or even its ruptures, exposing the collagen in intravascular subcutaneous tissue. Consequently, it will form platelet adhesion, aggregation, as well as thrombosis, which in turn causes coronary artery occlusion, acute coronary syndrome, and even serious irreversible myocardial ischemic injury. Therefore, MPO may reflect the same pathogenesis of acute myocardial ischemia such as cardiovascular partial activation of neutrophil activation, infiltration and degranulation and ischemia-reperfusion injury. Numerous clinical studies have shown that patients with acute coronary syndrome have significantly elevated levels of MPO in their blood serum. MPO is a new predictor for major adverse cardiovascular diseases of patients with ACS. MPO levels are a risk predictor of adverse cardiac events before AMI occurred. It had raised in first two hours of myocardial ischemia, in this period troponin remained within reference intervals. It shows the potential benefit of MPO on risk stratification of patients with chest pain. Thus, MPO levels can be used to determine treatment and prognosis of coronary heart disease.
Heart-type fatty acid binding protein (FABP3) is an important intracellular fatty acid binding protein with high cardiac specificity, and is present in large quantity in myocardial tissues. Myocardial cell permeability significantly changes during AMI. During the early stages of cell membrane breakage, FABP3 in the myocardial cells leaks into the extracellular fluid or blood circulation. FABP3 can be found in the blood as early as 1-3 hours after the onset of chest pain, 6-8 hours to reach the peak, and returns to normal level in the blood plasma within 24-30 hours. Studies have shown that the sensitivity and positive predictive value of FABP3 are significantly higher than those of cTnI within 3 hours of chest pain, excluded AMI patients without FABP3 changing. FABP3 can predict the risk of adverse cardiac events, as an early marker of AMI.
Cardiac troponin (cTn) is a structural protein composed of striated muscle. Its main function is to regulate myocyte contraction. CTn is composed of cardiac troponin T (cTnT), cardiac troponin I (cTnI) and troponin C (TnC). It plays an important role in the control of cardiac contractility. Blood levels of CTnI are generally lower than 0.3 μg/L in health. When critical myocardial ischemia occurred, myocardial cell membrane integrity gets destroyed, CTnI easily released into the blood since its small molecular weight, and increased after chest pain occurred 4-6 hours, which sustains for another 6-7 days. Because cardiac troponin only exists in cardiac muscles, it is the first choice for the evaluation of myocardial necrosis markers, and is the gold standard for detecting myocardial injury. Currently, cardiac troponin is mainly used for clinical diagnosis, risk assessment and prognosis of myocardial ischemic injury.
Current technologies for detecting MPO, FABP3, cTnI include ELISA, chemiluminescence, turbidimetric immunoassay and the colloidal gold lateflow immunoassay. Colloidal gold lateflow immunoassay requires less sample and is more easily operated, making it suitable for rapid detection of AMI. However, most colloidal gold lateflow immunoassay kits on the market only have a single indicator. Data obtained is usually simple, incomplete, has low detection sensitivity and specificity, and cannot fully reflect the situation of early myocardial infarction in patients, which makes it prone to misdiagnosis or delayed diagnosis. MPO can indicate risks 3 hours before AMI, but other indicators of inflammation can also lead to elevated MPO. On the other hand, FABP3 levels only change 1-3 hours after myocardial infarction and thus cannot be used as a predictor. CTnI is only detectable 4-6 hours after chest pain.
Currently, conventional triple test kit for clinical detects myoglobin, creatine kinase MB isoenzyme, and troponin. The capability of the tripe test kit is limited due to several reasons-late diagnosis, low accuracy, sensitivity, and poor specificity in early stage of AMI. Although troponin is the gold standard for the diagnosis of AMI, but only after 4-6 hours AMI troponin can be detected in serum. Due to the time lag, it is not an early marker of myocardial necrosis. This in turn has caused as many as 24% of patients to be misdiagnosed due to normal ECG and troponin assays. Similarly, CK-MB increased 4-8 hours after chest pain, and Myoglobin increased at 2-4 hours after infarction. Troponin and CK-MB elevated 4 hours after myocardial infarction, which makes it unable to provide early warning to AMI. Although Myoglobin is released into the blood two hours earlier than Troponin and CK-MB, it may raise in the condition of kidney or skeletal muscle damage, so it has poor cardiac specificity. As a consequence, triple test kit of AMI resulted in a number of patients to be misdiagnosed due to lack of sensitivity and specificity in early stage of AMI. The conventional kit can only show after myocardial infarction occurred not is a predictor of AMI.
Although ECG may also reflect the patient's condition, more than half of the patients who just start to experience chest pain have normal ECG results, thus resulting in their death due to delayed diagnosis.
Through examining existing products and literature, the detection of MYO, cTnI, CK-MB is characterized by time-lag and low accuracy in early stage of AMI; whereas existing technologies and product form for MPO, FABP3, cTnI detection can only be used as a single indicator and cannot act as a timely warning for developing AMI. Currently, MPO, FABP3 and cTnI are used in clinical practice in different product forms, thus have poor compatibility due to different production and procedures, making it difficult to detect the three indicators quickly.
This invention will bring about the following benefits: improved sensitivity of diagnosing for myocardial infarction, higher accuracy of diagnosing for myocardial infarction, an earlier diagnosis of diagnosing for myocardial infarction and dynamical monitoring the process and prognosis of myocardial infarction.